{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:10:17Z","timestamp":1793412617942,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to <jats:italic>n<\/jats:italic> = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study (<jats:italic>n<\/jats:italic> = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5\u201312 (mean difference of 26.0, 95% CI = 8.7\u201343.2, <jats:italic>p<\/jats:italic> = 0.008). In another single-arm study (<jats:italic>n<\/jats:italic> = 31), 32% (10\/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, <jats:italic>n<\/jats:italic> = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0\u201324.7, <jats:italic>p<\/jats:italic> = 0.01). In a pilot study (<jats:italic>n<\/jats:italic> = 15), the 7-day point prevalence of smoking abstinence at 26 weeks was 80% (12\/15), and at 52 weeks 67% (10\/15).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Only one RCT and three small clinical trials were identified assessing the efficacy of psilocybin combined with some form of psychotherapy in patients with alcohol and tobacco use disorder. All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate whether psilocybin-assisted therapy is effective in patients with SUD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2023.1134454","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T06:37:01Z","timestamp":1675924621000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":100,"title":["Therapeutic effect of psilocybin in addiction: A systematic review"],"prefix":"10.3389","volume":"14","author":[{"given":"Pim B.","family":"van der Meer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Fuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad A.","family":"Kaptein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan W.","family":"Schoones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen M.","family":"de Waal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke E.","family":"Goudriaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees","family":"Kramers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnt","family":"Schellekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metten","family":"Somers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs G.","family":"Bossong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Batalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1080\/09540261.2022.2040450","article-title":"Analysis of global prevalence of mental and substance use disorders within countries: focus on sociodemographic characteristics and income levels.","volume":"34","author":"Castaldelli-Maia","year":"2022","journal-title":"Int Rev Psychiatry."},{"key":"B2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S2215-0366(18)30337-7","article-title":"The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990&#x2013;2016: a systematic analysis for the global burden of disease study 2016.","volume":"5","author":"Degenhardt","year":"2018","journal-title":"Lancet Psychiatry."},{"key":"B3","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1176\/appi.ajp.2018.17101174","article-title":"Neuroscience of addiction: relevance to prevention and treatment.","volume":"175","author":"Volkow","year":"2018","journal-title":"Am J Psychiatry."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-011-0224-0","article-title":"New findings on biological factors predicting addiction relapse vulnerability.","volume":"13","author":"Sinha","year":"2011","journal-title":"Curr Psychiatry Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1037\/0022-006X.72.1.72","article-title":"Retrospective and prospective reports of precipitants to relapse in pathological gambling.","volume":"72","author":"Hodgins","year":"2004","journal-title":"J Consult Clin Psychol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00943","article-title":"Therapeutic use of LSD in psychiatry: a systematic review of randomized-controlled clinical trials.","volume":"10","author":"Fuentes","year":"2019","journal-title":"Front Psychiatry."},{"key":"B7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jcbs.2019.12.004","article-title":"The use of the psychological flexibility model to support psychedelic assisted therapy.","volume":"15","author":"Watts","year":"2020","journal-title":"J Contextual Behav Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1097\/01.NAJ.0000753464.35523.29","article-title":"Psychedelic-Assisted therapy: emerging treatments in mental health disorders.","volume":"121","author":"Penn","year":"2021","journal-title":"Am J Nurs."},{"key":"B9","doi-asserted-by":"publisher","first-page":"R63","DOI":"10.1016\/j.cub.2021.12.009","article-title":"Psychedelics.","volume":"32","author":"Kelmendi","year":"2022","journal-title":"Curr Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41573-022-00421-7","article-title":"The promises and perils of psychedelic pharmacology for psychiatry.","volume":"21","author":"McClure-Begley","year":"2022","journal-title":"Nat Rev Drug Discovery."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1021\/acschemneuro.8b00043","article-title":"Dark classics in chemical neuroscience: lysergic acid diethylamide (LSD).","volume":"9","author":"Nichols","year":"2018","journal-title":"ACS Chem Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1021\/acschemneuro.8b00186","article-title":"DARK classics in chemical neuroscience: psilocybin.","volume":"9","author":"Geiger","year":"2018","journal-title":"ACS Chem Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00213-021-06027-y","article-title":"Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review.","volume":"239","author":"Schimmel","year":"2022","journal-title":"Psychopharmacology."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104793","article-title":"Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review.","volume":"140","author":"van Elk","year":"2022","journal-title":"Neurosci Biobehav Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1177\/0269881112439253","article-title":"Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.","volume":"26","author":"Krebs","year":"2012","journal-title":"J Psychopharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1001\/archpsyc.1973.01750360040005","article-title":"Residential psychedelic (LSD) therapy for the narcotic addict. a controlled study.","volume":"28","author":"Savage","year":"1973","journal-title":"Arch Gen Psychiatry."},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.drugalcdep.2004.04.011","article-title":"Debating the controlled substances act.","volume":"76","author":"Spillane","year":"2004","journal-title":"Drug Alcohol Dependence."},{"key":"B18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1017\/S0033291721004207","article-title":"Why was early therapeutic research on psychedelic drugs abandoned?","volume":"52","author":"Hall","year":"2022","journal-title":"Psychol Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1177\/2045125316638008","article-title":"Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years.","volume":"6","author":"Dos Santos","year":"2016","journal-title":"Ther Adv Psychopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/acps.13249","article-title":"Therapeutic effects of classic serotonergic psychedelics: a systematic review of modern-era clinical studies.","volume":"143","author":"Andersen","year":"2021","journal-title":"Acta Psychiatr Scand."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13229","article-title":"Classic psychedelics and alcohol use disorders: a systematic review of human and animal studies.","volume":"27","author":"Calleja-Conde","year":"2022","journal-title":"Add Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.","volume":"10","author":"Page","year":"2021","journal-title":"Systematic Rev."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials.","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1177\/0269881114565144","article-title":"Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.","volume":"29","author":"Bogenschutz","year":"2015","journal-title":"J Psychopharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1001\/jamapsychiatry.2022.2096","article-title":"Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial.","volume":"79","author":"Bogenschutz","year":"2022","journal-title":"JAMA Psychiatry."},{"key":"B27","article-title":"Preliminary report on the experience with psychosomimetic drugs in the treatment of alcoholism.","volume":"10","author":"Rydzy\u0144ski","year":"1968","journal-title":"Act Nerv Super (Praha)."},{"key":"B28","first-page":"81","article-title":"Treatment of alcoholism with psychotomimetic drugs. a follow-up study.","volume":"20","author":"Rydzy\u0144ski","year":"1978","journal-title":"Act Nerv Super (Praha)."},{"key":"B29","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1177\/0269881114548296","article-title":"Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.","volume":"28","author":"Johnson","year":"2014","journal-title":"J Psychopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3109\/00952990.2016.1170135","article-title":"Long-term follow-up of psilocybin-facilitated smoking cessation.","volume":"43","author":"Johnson","year":"2017","journal-title":"Am J Drug Alcohol Abuse."},{"key":"B31","first-page":"5","article-title":"Psilocybin and chronic alcoholism.","volume":"32","author":"Albuquerque Fortes","year":"1966","journal-title":"Arquivos Coordenadoria Saude Mental Estado Sao Paulo."},{"key":"B32","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1177\/002076406701300205","article-title":"Theoretical aspects of L.S.D. therapy.","volume":"13","author":"Buckman","year":"1967","journal-title":"Int J Soc Psychiatry."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1080\/17512433.2021.1933434","article-title":"Blinding and expectancy confounds in psychedelic randomized controlled trials.","volume":"14","author":"Muthukumaraswamy","year":"2021","journal-title":"Exp Rev Clin Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.724606","article-title":"Psychedelics and neuroplasticity: a systematic review unraveling the biological underpinnings of psychedelics.","volume":"12","author":"de Vos","year":"2021","journal-title":"Front Psychiatry."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/s41386-022-01297-2","article-title":"Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects.","volume":"47","author":"Holze","year":"2022","journal-title":"Neuropsychopharmacology."},{"key":"B36","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1177\/0269881121991822","article-title":"Optimal dosing for psilocybin pharmacotherapy: considering weight-adjusted and fixed dosing approaches.","volume":"35","author":"Garcia-Romeu","year":"2021","journal-title":"J Psychopharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1177\/0269881117731279","article-title":"Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.","volume":"32","author":"Griffiths","year":"2018","journal-title":"J Psychopharmacol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81446-7","article-title":"Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.","volume":"11","author":"Kaertner","year":"2021","journal-title":"Sci Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1038\/s41386-019-0317-8","article-title":"Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant.","volume":"44","author":"Wilkinson","year":"2019","journal-title":"Neuropsychopharmacology."},{"key":"B40","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1176\/appi.ajp.2021.21030277","article-title":"Adjunctive ketamine with relapse prevention\u2013based psychological therapy in the treatment of alcohol use disorder.","volume":"179","author":"Grabski","year":"2022","journal-title":"Am J Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62878","article-title":"Self-blinding citizen science to explore psychedelic microdosing.","volume":"10","author":"Szigeti","year":"2021","journal-title":"eLife."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00247-4","article-title":"Cannabis use and cannabis use disorder.","volume":"7","author":"Connor","year":"2021","journal-title":"Nat Rev Dis Primers."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1134454\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T06:37:06Z","timestamp":1675924626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1134454\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":42,"alternative-id":["10.3389\/fpsyt.2023.1134454"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2023.1134454","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]},"article-number":"1134454"}}